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Updated: Oct 1, 2026

Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
Published on: June 24, 2012
The group-specific murine coronavirus genes are not essential, but their deletion, by reverse genetics, is
Cornelis A M de Haan1, Paul S Masters, Xiaolan Shen
1Virology Division, Utrecht University, Utrecht, The Netherlands. x.haan@vet.uu.nl
Abstract:
In addition to a characteristic set of essential genes coronaviruses contain several so-called group-specific genes. These genes differ distinctly among the three coronavirus groups and are specific for each group. While the essential genes encode replication and structural functions, hardly anything is known about the products and functions of the group-specific genes. As a first step to elucidate their significance, we deleted the group-specific genes from the group 2 mouse hepatitis virus (MHV) genome via a novel targeted recombination system based on host switching (L. Kuo, G. J.Godeke, M. J. Raamsman, P. S. Masters, and P. J. M. Rottier, 2000, J. Virol. 74, 1393-1406). Thus, we obtained recombinant viruses from which the two clusters of group-specific genes were deleted either separately or in combination in a controlled genetic background. As all recombinant deletion mutant viruses appeared to be viable, we conclude that the MHV group-specific genes are nonessential, accessory genes. Importantly, all deletion mutant viruses were attenuated when inoculated into their natural host, the mouse. Therefore, deletion of the coronavirus group-specific genes seems to provide an attractive approach to generate attenuated live coronavirus vaccines.
Insights
Mouse hepatitis virus (MHV) group-specific genes are nonessential and can be deleted. Deleting these genes from MHV creates attenuated viruses, suggesting potential for live coronavirus vaccines.
Area of Science:
- Virology
- Molecular Biology
- Vaccine Development
Background:
- Coronaviruses possess essential genes for replication and structure, alongside group-specific genes with unknown functions.
- These group-specific genes vary significantly across coronavirus groups and are unique to each.
- The functions of coronavirus group-specific genes remain largely uncharacterized.
Purpose of the Study:
- To investigate the significance of group-specific genes in the group 2 mouse hepatitis virus (MHV).
- To generate recombinant MHV lacking group-specific genes to assess their necessity and function.
- To evaluate the potential of MHV group-specific gene deletion for vaccine development.
Main Methods:
- Utilized a novel host-switching-based targeted recombination system to delete group-specific genes from the MHV genome.
- Created recombinant viruses with separate or combined deletions of the two group-specific gene clusters.
- Assessed the viability of the resulting recombinant deletion mutant viruses.
Main Results:
- All generated recombinant deletion mutant viruses were viable, indicating group-specific genes are nonessential.
- The deletion of group-specific genes resulted in the attenuation of MHV in its natural host, the mouse.
- MHV group-specific genes were confirmed as accessory genes.
Conclusions:
- The group-specific genes of MHV are nonessential and can be deleted without compromising viral viability.
- Deletion of these genes leads to viral attenuation, presenting a promising strategy for developing live attenuated coronavirus vaccines.
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